Background: Opioid analgesics are commonly used for chronic non-cancer pain but may impair gonadal and adrenal axis function. We measured pituitary function, rates of hormone deficiency, sexual function and quality of life (QoL) in patients on oral or transdermal opioids versus age and sex-matched controls.
Methods: Participants with chronic non-malignant pain receiving oral or transdermal opioids for more than six months and matched controls provided morning (before 0900 h) blood samples and completed validated questionnaires for general health, sexual function, fatigue and quality of life. Participants with morning serum cortisol levels <250 nmol/L underwent 250 μg short Synacthen test (SST) and overnight metyrapone test (OMT).
Results: Forty patients treated with opioids (M:25, F:15) and 25 age matched controls (M:14, F:11) were studied. BMI was significantly higher among the opioid users (P<0.01). There was no difference between opioid users and controls in mean morning cortisol in the overall group or testosterone among the men. However opioid users had a significantly higher rate of adrenal insufficiency (AI) defined by morning cortisol <250 nmol/L AND failing either the SST or OMT 9/40 vs 0/25 P=0.01. Median morphine equivalent daily dose was higher in opioid users with AI (100 mg vs 60 mg, P<0.05). There was a significant negative correlation between BMI and serum testosterone among male participants (R=−0.50, P=0.001). Multiple regression analysis showed a significant effect of BMI (P=0.002) but not opioid use (P=0.29). However, there was a small sub-group of male opioid users (n=6) whose testosterone lay below the expected level for BMI. Opioid treated patients scored significantly lower on all QoL and sexual function measures.
Conclusion: A significant proportion of oral/transdermal opioid users are at risk of adrenal insufficiency. BMI confounds assessment of testosterone deficiency. Further data are required to determine optimal management strategies, including opioid reduction, opioid rotation, or hormone replacement.